Disease spectrum of patients with antineutrophil cytoplasmic autoantibodies of defined specificity: distinct differences between patients with anti‐proteinase 3 and anti‐myeloperoxidase autoantibodies

Abstract

Franssen C, Gans R, Kallenberg C, Hageluken C, Hoorntje S (University Hospital, Groningen; Free University Hospital, Amsterdam; and Catharina Hospital, Eindhoven; the Netherlands). Disease spectrum of patients with antineutrophil cytoplasmic autoantibodies of defined specificity: distinct differences between patients with antiproteinase 3 and antimyeloperoxidase autoantibodies. J Intern Med 1998; 244: 209–16. Objective To compare the disease spectrum of consecutive patients with antineutrophil cytoplasmic autoantibodies directed against proteinase 3 (anti‐PR3) or myeloperoxidase (anti‐MPO). Design Retrospective analysis. Setting Three teaching hospitals in the Netherlands. Main outcome measures Clinical features at presentation, histopathological characteristics and outcome. Subjects All consecutive patients who tested positive for anti‐PR3 (n= 46) or anti‐MPO (n= 46) over an 8‐year‐period. Results At diagnosis, patients with anti‐PR3 had a higher vasculitis activity index than patients with anti‐MPO (P < 0.001). The mean (SD) number of affected organs in the anti‐PR3 group exceeded that of the anti‐MPO group (3.9 (1.4) and 2.2 (1.1), respectively; P < 0.01). The combination of renal and respiratory tract involvement was present in as many as 78.3% of patients with anti‐PR3 and in only 23.9% of patients with anti‐MPO (P < 0.01). Renal‐limited disease exclusively occurred in patients with anti‐MPO. Granulomas were found in 41.3% of anti‐PR3‐ but in only 4.3% of anti‐MPO‐positive patients (P < 0.01). All anti‐PR3‐positive patients had Wegener's granulomatosis or microscopic polyangiitis. By contrast, diagnoses in the anti‐MPO group were more diverse: idiopathic necrotizing crescentic glomerulonephritis (26.1%), microscopic polyangiitis (26.1%), Churg–Strauss syndrome (4.3%), Wegener's granulomatosis (2.2%), giant cell arteritis (2.2%), clinically suspected vasculitis (19.6%), as well as miscellaneous nonvasculitic disorders (19.6%). During follow‐up, 10 anti‐PR3‐positive patients had 11 relapses whereas only 3 patients with anti‐MPO relapsed (P= 0.04). Conclusion A large divergence was seen in the disease spectrum between patients with anti‐PR3 and those with anti‐MPO. In particular, extra‐renal disease manifestations, granuloma formation and relapses were more prominent in anti‐PR3‐ than in anti‐MPO‐positive patients.

Myeloperoxidase Positive Wegener’s Granulomatosis with Isolated Otorhinological

“…In contrast, the patient we present was diagnosed swiftly, in under 5 weeks. Patients with MPO positive GPA have also been found to present at a later age than their PR3 positive counterparts -median age of 63 versus 56 [6]. This is in keeping with our patient, who was 71 years old at the time of diagnosis.…”

“…A difference in T-cell mediated immunity between patients with anti-PR3 and anti-MPO has also been speculated to play a role in the observed higher frequency of granuloma formation in anti-PR3 than anti-MPO patients. This could be due to the fact that PR3 reactive T-cells were observed more frequently in patients with PR3 than in controls, whereas MPO-reactive T-cells were observed at the same frequency in anti-MPO patients and in controls [6].…”

Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody–associated vasculitis

“…The patients in the present trial were almost exclusively diagnosed as having WG, with the majority of cases associated with cANCA positivity. Recently, a higher relapse rate in WG compared with MPA in PR3 cANCA-positive disease compared with MPO pANCA-positive disease has been reported by several groups (16,29,30).…”

Anca-Associated Glomerulonephritis: Relationship of Main Anca Subtypes to Renal Outcome, Age and Sex of the Patients

“…5 Nonetheless, cANCA pattern is highly specific for Wegener's granulomatosis, whereas pANCA is found in the sera of patients with vasculitis, glomerulonephritis and several other diseases. 6,23 Also, race is an important prognostic factor for renal survival. 5 The poor renal survival in our patients with pANCA compared with those with cANCA might have stemmed from disparities in genetic factors and/or spectrum of underlying disease associated with the main subtypes of ANCA in different nations.…”

“…3 Yet, in previously published series, the effect of the main ANCA subtypes on renal outcome and its relationship to demographic findings and clinical features of patients with ANCA-associated glomerulonephritis has been associated with conflicting results. [3][4][5][6][7][8][9] This prospective study was carried out to answer two questions : 1) what is the effect of ANCA main subtypes on the renal prognosis of patients with ANCAassociated glomerulonephritis; and 2) what are the age-and sex-related differences between the two types of pANCA and cANCA-associated glomerulonephritis.…”